The primary objective of this randomized controlled clinical study is to evaluate the peri-procedural safety and potential effectiveness (mechanistic effect) of implanting the IASD System II in heart failure patients with an LV ejection fraction…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety
Peri-procedural, and 1 month Major Adverse Cardiac, Cerebrovascular, and Renal
Events (MACCRE)
The primary safety outcome measure is the incidence of one or more of the
following major adverse cardiac, cerebrovascular embolic, or renal
events (MACCRE) defined as:
1. Cardiovascular death through 1-month post implant;
2. Embolic stroke through 1-months post implant;
3. Device and or procedure related adverse cardiac events through 1-month post
implant;
4. New onset or worsening of kidney dysfunction (defined as eGFR decrease of >
20 ml/min) through 1-month post implant
Effectiveness
1. Change in supine exercise PCWP at 1 month, as assessed by an independent
blinded hemodynamic core laboratory, across the four
values measured at each visit (values at 20W, 40W, 60W and 80W).
Secondary outcome
1. Change in exercise PEAK PCWP from baseline at 1 month.
2. Cardiovascular death through 12 months;
3. Rate of total (first plus recurrent) HF admissions/emergency clinic visits
or acute care facilities for IV diuresis for HF through 12 months;
4. Change in QOL (EQ-5D, and KCCQ score) at 12 months
Additional Outcome Measures
Safety related outcome measures:
1. Major adverse cardiac events through 12-months
2. All serious adverse events (SAEs) through 12-months
3. All-cause mortality, CV mortality and heart failure related mortality
through 12-months
4. Newly acquired persistent or permanent AF or atrial flutter through
12-months
5. Implant embolization and clinically significant device migration through
12-months.
6. Systemic embolic events through 12-months.
7. Increase in RV size/decrease in RV function through 12-months
8. The need for implant removal or occlusion of the implant.
Efficacy related outcome measures:
1. All-cause, and heart failure related hospitalizations/emergency department
visits with IV treatment for HF; and number of hospitalization days, ICU days
through 12 months
2. Treatment for outpatient worsening of heart failure
3. Days alive, and not-hospitalized through 12-months
4. Change in blinded Investigator assessed NYHA classification between baseline
and 12 months.
5. Change in 6MWT distance between baseline and 12 months
6. Assessment of shunt dimensions and flow at 12 months
7. Changes in resting and exercise PA pressures and CI between baseline and 1
month as assessed by an independent blinded hemodynamic core laboratory.
8. Change in BNP and/or NT-pro-BNP between baseline and at 12 months. MR-ANP is
optional.
9. Changes in LA, LV dimensions, volume, and function, between baseline and 12
months assessed by an independent echocardiographic core laboratory
10. Changes in RA, LA, LV and RV dimensions, volume, and function between
baseline and 12 months assessed by a cardiac MRI core laboratory (Sub-study
only)
11. Change in CPET parameters (including exercise time) between baseline and 12
months as assessed by an independent blinded CPET core laboratory (Sub-study
only)
12. Change in diuretic medications between baseline and 12 months
Background summary
Heart failure is defined as a disorder of the heart pump function with
associated symptoms. Symptoms can be very different, but include at
least his fatigue and / or dyspnea.
Mortality is high and depending on the severity of the heart failure. Fifty
percent of patients deceased within five years (with severe heart
failure, within one year) after diagnosis.
The prevalence of heart failure among the population is 2-2.5%. Currently there
are 200,000 patients with heart failure in the Netherlands. The
prevalence increases sharply with increasing age.
With increasing aging population combined with improved medical techniques of
cardiac and non-cardiac diseases, the prevalence of heart
failure is increasing.
This study is evaluating a new device (Inter-atriale septum Device (IASD)
System II) that is permanently implanted in the heart and is designed
to reduce the increased pressure due to heart failure, by creating a small
permanent opening between the two upper chambers in the heart. The
relief of this pressure by the study device may reduce some or all of the
symptoms a subject is experiencing.
Study objective
The primary objective of this randomized controlled clinical study is to
evaluate the peri-procedural safety and potential effectiveness (mechanistic
effect) of implanting the IASD System II in heart failure patients with an LV
ejection fraction >=40%, elevated left sided filling pressures, and who remain
symptomatic despite optimal Guideline Directed Medical Therapy (GDMT). Clinical
outcomes will also be evaluated. A subset of the results of this study will be
used to facilitate design of the U.S. pivotal trial.
Study design
Multicenter, Prospective, Randomized Controlled, Single (patient) Blinded
Trial, with Non-implant Control group; 1:1 randomization. Patients
will be followed for 1 year, and annually every 12 months for a total of 5
years after index procedure and implant.
Intervention
Percutaneous implantation (permanent) of the IAS System II.
Study burden and risks
Heart Catheterization Risks
The main risks of a heart catheterization include but are not limited to :
• pain at the catheter insertion site,
• abnormal heart rate,
• excessive collection of blood at insertion site (4 cases in previous studies
of excessive collection of blood at insertion site),
• fever after the procedure,
• significantly increased or decreased blood pressure sometimes requiring
medication,
• blood loss sometimes requiring blood replacement,
• allergic reaction to the dye used to take pictures of the heart,
• temporary stoppage of breathing,
• reaction to the anesthesia medications,
• accidental creation of an abnormal passage between an artery and vein,
• obstruction of a blood vessel by an air bubble,
• blockage of a blood vessel by a blood clot,
• injury to a nerve at the insertion site, appearance of a bulge in a blood
vessel,
• and the tearing or poking of a hole through a blood vessel or heart (2 cases
in previous studies of tearing or poking of a hole through a blood
vessel).
These risks are uncommon. This procedure will be performed 2 times within
approximately 1 month. To reduce the likelihood of these risks,
the study sponsor carefully selects and supports study doctors that have
significant experience with similar types of procedures.
Intra-cardiac Echocardiography Risks
The main risks of an intra-cardiac echo include but are not limited to
irregular heart rhythms, which may require treatment, bleeding where the
catheter was put into your blood vessel, a blood clot could form, and the
catheter may damage a blood vessel, for example, where the catheter
was inserted. Other potential risks of intra-cardiac echo are puncture of a
blood vessel as it travels to the heart or puncture of the heart, both of
which may be life threatening and may require urgent surgery to correct. While
uncommon, a heart attack or stroke might be triggered by the
test. To reduce the likelihood of these unlikely risks, specially trained
doctors perform these procedures.
Investigational Device and Implantation Procedure Risks
The main risks of having the investigational device implanted are similar to
the risks listed above for heart catheterization. In addition, small
clots may form on the implant itself and be released into the blood
circulation. There is also a risk of paradoxical embolism, where the blood
clot moves directly from the right side of the heart to the left through the
hole made by the device. If clots like these happen, stroke, heart
failure, heart attack or death may occur. The study doctor will give the
patient medications before the procedure, (anticoagulation also called
blood thinner), after the procedure and during the study follow up period to
reduce this risk. Some preclinical testing without anticoagulation
suggested that thrombus (clot) formation might occur. Therefore, this device
should not be used in patients who cannot be anticoagulated
(e.g., with heparin or another type of anticoagulant).
Another potential risk is that, once implanted in the heart, the
investigational device does not stay in place and floats away into another part
of
the heart or into a blood vessel. If this happens, stroke, heart failure, heart
attack or death may occur. To reduce the risk of this happening, the
study doctor uses special imaging equipment during the procedure to see the
investigational device and make sure it is placed in the correct
position in the heart. In addition, the investigational device shape and
materials were selected to hold it in place. If the device does move out of
place during the implant procedure, the study doctor may use a catheter to
retrieve and remove it (in previous studies, 2 of 75 were not in the
correct position during procedure. The devices were removed and a new device
successfully implanted during the same procedure). If the
device moves out of place after the subject is discharged from the hospital,
the investigational device may need to be removed during open
heart surgery (this has not yet occurred in previous studies).
Another potential risk is that one or more of the investigational device arms
rubs or erodes or pokes a hole into a blood vessel or part of the
heart, also referred to as perforation or erosion. If this happens, urgent
surgery may be required to remove the device and repair the tear or
hole.
Another potential risk is a break of one of the investigational device arms
once it is in the heart. If this happens, the broken arm could rub
against the wall of the heart causing a callous, blood clot and/or infection.
In the unlikely event that the investigational device breaks into
several pieces, a piece of it could potentially break off and float away to
another place in the body. Depending on its final location, surgery may
be required to remove the piece and the remaining broken device. To reduce the
risk of this happening, the investigational device is made of
materials that were specifically selected because of their strength and
resistance to wear.
Another potential risk is that the heart failure does not improve during the
study, or worsens. The procedure may involve risks which are
currently unforeseeable.
Side effects are usually temporary and manageable. However, it is possible they
could cause serious injury or death. The patient's condition
may not get better or may become worse during this study. If we learn of any
new risks while this study is ongoing, the study doctor will make
the patient aware of them as soon as possible.
Exercise Testing Risks
The peak oxygen test can be exhausting. The risks of these exercise stress
tests include brief light-headedness, severe shortness of breath,
fatigue (tiredness) from walking on the treadmill or pedaling the exercise
bike, muscle soreness, irregular heartbeat, chest pain, sudden heart
attack, stroke, or death. To minimize these risks trained medical professionals
will be present during this procedure. In addition, the patient will
have his/ her heart rate monitored continuously throughout the testing. The
patient will also have his/ her blood pressure and his/ her rate of
perceived exertion monitored throughout the testing.
Blood Draw Risks
There are some side effects that can happen when the patient has his/ her blood
drawn. This includes excessive bleeding, fainting or feeling
light-headed, hematoma (blood pooling under the skin), infection (a slight risk
any time the skin is broken).
Pregnant women
This treatment may have unforeseeable risks to your embryo or foetus if you are
pregnant at the moment of the procedure. Woman of
childbearing age and fertile are not authorized to take part of this clinical
trial.
Risks of Antiplatelet Medication
The medications used to reduce the chance of developing a blood clot do carry
certain risks. Sometimes the medications can cause bleeding
problems, headaches, dizziness, pain, and discomfort. Other risks include
bruises, swelling, blood in the urine or stool or stools that look like
coffee grounds, more bleeding than normal during your period, purple toes, a
sign of purple toes syndrome, a serious condition; and pain,
change in temperature, or noticeable blackish areas in your extremities.
Cardiac MRI Risks
The magnetic resonance imaging (MRI) machine uses a strong magnet to take
images of the heart. Due to the use of the strong magnet,
special precautions must be taken to perform an MRI on people with certain
implanted devices such as pacemakers or cochlear implants, or
other internal metal objects, such as surgical clips, plates, screws, or wire
mesh. The MRI magnet may cause any metal in the body to move.
The patient will be screened carefully beforehand to make sure you can have an
MRI. There are no other known risks of MRI. Some
individuals with claustrophobia (fear of closed spaces) may find the MRI
equipment too confining. In that case, the patient can request to be
removed from the scanner and this will be done immediately. The MRI scanner
makes a loud thumping sound. The patient can ask to wear
protective earplugs during the scanning.
Benefits
There is no guarantee that the subject will benefit from participation in this
study.
Potential benefits to patients implanted with the study device include the
following:
• Reduction in shortness of breath
• Reduction in the number of hospitalizations and/or hospital days
• Reduction in the number of emergency room visits
• Reduction in medications
• Improved exercise tolerance
• Improved quality of life
• Improved life expectancy
By participating in this study, the subject will help others by providing
information that may be used to develop new treatments for patients with
similar conditions.
One Highwood Drive One Highwood Drive One Highwood Drive One Highwood Drive
01876 Tewksbury 01876 Tewksbury
US
One Highwood Drive One Highwood Drive One Highwood Drive One Highwood Drive
01876 Tewksbury 01876 Tewksbury
US
Listed location countries
Age
Inclusion criteria
1. Chronic symptomatic heart failure (HF) documented by the following:
a. New York Heart Association (NYHA) class III/ambulatory class IV symptoms (Paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening visit; or signs (Any rales post cough, chest x-ray demonstrating pulmonary congestion,) within past 12 months; AND
b. >= One hospital admission for which HF was a major component of the hospitalization, or a healthcare facility (emergency department/acute care facility) treatment with intravenous (IV) or intensification of oral diuresis for HF, within the 12 months prior to study entry; OR an NT-pro BNP value > 200 pg/ml in normal sinus rhythm, > 600 pg/ml in atrial fibrillation, or a BNP value > 70 pg/ml in normal sinus rhythm, > 200 pg/ml in atrial fibrillation within the past 6 months.
2. Ongoing stable GDMT HF management and management of potential comorbidities according to the 2013 ACCF/AHA Guidelines for the management of Heart Failure (with no significant changes [>100% increase or 50% decrease], excluding diuretic dose changes for a minimum of 4 weeks prior to screening) that is expected to be maintained without change for 6 months.
3. Age >= 40 years old
4. Site determined LV ejection fraction >= 40% within the past 3 months, without previously documented ejection fraction <30%.% (within the last 5 years).
5. Site determined elevated left atrial pressure with a gradient compared to right atrial pressure (RAP) documented by:
a. End-expiratory PCWP during supine ergometer exercise >= 25mm Hg, and greater than RAP by >= 5 mm Hg.
6. Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following:
a. LA diameter > 4 cm; or
b. LA volume index > 28 ml/m2 or
c. Lateral e* <10 cm/s; or
d. Septal e* <8 cm/s; or
e. Lateral E/e* >10 ; or
f. Septal E/e* > 15
7. Subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the IRB or EC
8. Subject is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams
9. Trans-septal catheterization and femoral vein access is determined to be feasible by site principal interventional cardiology investigator
Exclusion criteria
1. Myocardial infarction and/or percutaneous cardiac intervention within past 3 months; CABG in past 3 months, or current indication for coronary revascularization
2. Cardiac resynchronization therapy initiated within the past 6 months
3. Severe heart failure defined as one or more of the below:
a. ACC/AHA/ESC Stage D heart failure, Non-ambulatory NYHA Class IV HF;
b. Cardiac index < 2.0 L/min/m2
c. Inotropic infusion (continuous or intermittent) within the past 6 months
d. Patient is on the cardiac transplant waiting list
4. Inability to perform 6 minute walk test (distance < 50 m), OR 6 minute walk test > 600m
5. Known clinically significant un-revascularized coronary artery disease, defined as: epi-cardial coronary artery stenosis associated with angina or other evidence of coronary ischemia.
6. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months
7. Known clinically significant untreated carotid artery stenosis.
8. Presence of significant valve disease defined by the site cardiologist as:
a) Mitral valve regurgitation defined as grade >= 3+ MR
b) Tricuspid valve regurgitation defined as grade >= 2+ TR;
c) Aortic valve disease defined as >= 2+ AR or > moderate AS
9. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or other infiltrative cardiomyopathy (e.g. hemochromatosis, sarcoidosis)
10. Subject is contraindicated to receive either dual antiplatelet therapy or warfarin (analogue); or has a documented coagulopathy
11. Atrial fibrillation with resting HR > 100 BPM
12. Arterial oxygen saturation < 95% on room air
13. Significant hepatic impairment defined as 3X upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
14. Right ventricular dysfunction, defined by the site cardiologist as
a. More than mild RV dysfunction as estimated by TTE; OR
b. TAPSE < 1.4 cm; OR
c. RV size >= LV size as estimated by TTE; OR
d. Echocardiographic or clinical evidence of congestive hepatopathy; OR
e. Evidence of RV dysfunction defined by TTE as an RV fractional area change < 35%;
15. Resting RAP > 14 mmHg
16. Evidence of pulmonary hypertension with PVR > 4 Wood units
17. Chronic pulmonary disease requiring continuous home oxygen, OR hospitalization for exacerbation in the 12 months prior to study entry, OR significant chronic pulmonary disease defined as FEV1 < 50% predicted, or in the opinion of the investigator
18. Currently participating in an investigational drug or device study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational trials
19. Life expectancy less than 12 months for non-cardiovascular reasons
20. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation
21. Known or suspected allergy to nickel
22. Fertile women
23. Currently requiring dialysis; or estimated-GFR <25ml/min/1.73 m2 by CKD-Epi equation
24. Systolic blood pressure >170 mm Hg at screening
25. Subjects with existing atrial septal defects. Subjects with a patent foramen ovale (PFO), who meet PCWP criteria despite the PFO, are allowed.
26. Subjects on immunosuppression or systemic steroid treatment (>10 mg prednisone/day).
27. Severe obstructive sleep apnea not treated with CPAP or other measures
28. Severe depression and/or anxiety
29. In the opinion of the investigator, the subject is not an appropriate candidate for the study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02600234 |
| CCMO | NL57357.042.16 |